alexa Computational Study On Halogen Bonding Interaction Of MDM2 Inhibitors
ISSN: 2161-0444

Medicinal Chemistry
Open Access

Like us on:
OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations

700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)

Share This Page

Additional Info

Loading Please wait..

3rd International Conference on Medicinal Chemistry & Computer Aided Drug Designing
December 08-10, 2014 DoubleTree by Hilton Hotel San Francisco Airport, USA

Yujing Zhou and Ming Wah Wong
Accepted Abstracts: Med Chem
DOI: 10.4172/2161-0444.S1.013
p53, as ?guardian of the genome?, plays a very important role in cells. It acts as a transcription factor and more importantly as a tumor suppressor protein. High level of wild-type p53 shows growth-inhibitory properties. The level of p53 in cells is negatively regulated by MDM2 via an auto regulatory feedback loop. However, in many tumor cells, MDM2 is overexpressed and highly impair the function of p53 to suppress tumor. Thus design and development of effective inhibitors to block p53 and MDM2 interactions offer a novel strategy to conquer cancer. Since most of the research up to now lacks the understanding of the nature chemistry of the binding, this study is focused on better understanding the chemistry of the interaction between MDM2 and its inhibitors, especially the halogen bonding interaction. From our docking studies of ligand RG7112, a nutlin derivative inhibitor for MDM2 in clinical trial phase one, using the Molecular Operating Environment, a group of key residues, Lys51, Phe55, Gly58, Tyr67, Val93 and His96, were identified to serve as pharmacophore and provides useful information for future design and optimization of potent ligands. Among the key residues, His96 was observed to provide two important interactions, which are halogen bonding between phenyl-chloride atom and His96 backbone oxygen atom, and CH-π interaction between the phenyl ring and His96 histidine ring. From the comparison docking of a group of chlorinated and non-chlorinated MDM2 ligands, the docking scores were shown to be better for chlorinated inhibitors than non-chlorinated. In addition, the docking poses of all non-chlorinated inhibitors solidified our hypothesis, as for non-chlorinated ligands, the binding towards receptor were quite loose, and the inhibitors may not even be maintained in the pocket region. Furthermore, a set of docking studies of chlorinated, brominated and iodinated RG7112 fragments was done. Space filling model of the best poses showed close contact between inhibitors and His96 groups, with distance between halogen atoms and His96 oxygen 3.6-4?, with a score following halogen bonding strength trend I>Br>Cl, In addition, the phenyl rings of the inhibitors and the His96 histidine ring were identified in a good orientation to form CH-π interaction which may also contribute to the binding efficiency, and this finding prove by a set of docking for non-benzyl RG7112 fragments, showing that without the phenyl rings, the inhibitors were still bounded within the pocket region, but would not be deep enough into the pocket and with worse docking scores. Thus we may make the conclusion that the halogen bonding between the phenyl-halogen atoms and His96 backbone oxygen helps the ligands bind to the pockets, and the CH-π interaction between phenyl rings and His96 histidine ring helps to refine the pose orientation, to produce tighter binding. The two key interactions above contribute together and are critical for the binding of ligands towards MDM2 receptor.
image PDF   |   image HTML
Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

1-702-714-7001Extn: 9037

Business & Management Journals


1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

1-702-714-7001Extn: 9042

General Science

Andrea Jason

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

1-702-714-7001Extn: 9042

© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version